Continued progress in the management of bladder cancer will require the use of effective chemotherapy both as systemic therapy combined with surgery and/or radiation for advanced local or metastatic disease and as intravesical administration for superficial bladder cancer. Bladder cancers induced in syngeneic mice by the urothelial carcinogen N-(4-(5-nitro-2-futyl)-2-thiazolyl) formamide (FANFT) have been used to screen drugs for activity. FANFT-induced tumors resemble their human counterpart grossly and histologically. Early generation transitional and squamous cell tumor transplants will continue to be established. The responsiveness of each tumor line to single and combination chemotherapy as well as sequential therapy will be evaluated. Primary FANFT-induced tumors most simulate the disease in man. Single and combination regimens will be given to mice injesting FANFT and their effectiveness in reducing the icidence, size, and stage of bladder tumors will be determined. The effect of therapy on survival will be separately studied. Intravesical agents will be evaluated by determining: (1) Which drugs are capable of inhibiting the implantation of cauterized bladder tumor cells on the urothelial surface; and (2) The relative efficacy of antitumor drugs in reducing the incidence or stage of primary FANFT-induced bladder cancer. Therapy will be initiated when mice have dysplasia/carcinoma in situ. Techniques to enhance the activity of intravesical chemotherapy will be evaluated. The in vitro responsiveness of several bladder cancer cell lines to a battery of antitumor drugs will be evaluated. The results will be compared to the activity of these drugs to the same tumors in vivo. Both a 7-day in vitro assay and the tumor stem cell assay will be used and compared.